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Since the pioneer work published by Takahashi & Yamanaka, the technique of reprogramming cells from a differentiated to an embryonic-like status has experienced an exploding development in regard to both techniques and applications. The most obvious application is the use in tissue regeneration. However, two key obstacles need to be overcome for clinical realization, i.e. risk of reprogrammed cells to develop neoplasiae as well as cumbersome and costly cell culture procedures. Therefore, it is imperative to develop cost-efficient methods with a lower the risk of cancer.
The present invention has solved this problem by using a modification of the originally described method. Here, the transcription factors Sox2, cMyc and Klf4 are exogenously and stably expressed, whereas Oct4 is introduced with an exogenous transient expression system.
This method is qualified to produce autologous neural stem cells that proliferate indefinitely and are able to re-differentiate into functional neural cells. The technology therefore applies to the tissue regeneration of neural tissue and disease modelling, especially in the central nervous system.
A European patent application has been filed: Nr. 13 707 277.3 “induced neural stem cells”.
On behalf of the University of Bonn, PROvendis offers access to the technology under a License Agreement.
Thier M, et al. (2012) Direct conversion of fibroblasts into stably expandable beural stem cells. Cell Stem Cell 10: 473-9.
Lujan E, et al. (2012) Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. Proc. Natl. Acad. Sci. USA 109(7): 2527-32.
Kim J, et al. (2011) Direct reprogramming of mouse fibroblasts to neural progenitors. Proc. Natl. Acad. Sci. USA 108(19): 7838-43.
Takahashi K & Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663-76.